28- Cushing's Syndrome Flashcards
what is Cushing’s syndrome?
disorder characterised by prolonged exposure to high/ excess cortisol
commonly due to iatrogenic causes - prolonged use of high-dose glucocorticoid therapy - as well as primary and secondary causes
how do exogenous glucocorticoids contribute to iatrogenic Cushing’s syndrome?
exogenous glucocorticoids activate cortisol receptors in the body
lead to strong negative feedback inhibition of the HPA axis at high doses = suppress CRH and ACTH release
what happens to adrenal function with prolonged high-dose glucocorticoid therapy? (Cushing’s)
adrenal cortex stops producing cortisol and adrenal androgens - can lead to adrenal atrophy due to the lack of stimulation by ACTH
why is discontinuing exogenous glucocorticoids challenging? how should it be discontinued? (Cushing’s)
requires a gradual tapering off process instead of abrupt withdrawal
the hypothalamus and pituitary start producing CRH and ACTH but it takes several days for the adrenal glands to become responsive to ACTH again due to atrophy/suppression during therapy
what is Cushing’s disease?
a specific form of Cushing’s syndrome = excess cortisol production caused by an anterior pituitary adenoma secreting ACTH
how does an anterior pituitary adenoma contribute to Cushing’s disease? how does this impact the negative feedback loop?
anterior pituitary adenoma produces excess ACTH = increased cortisol and adrenal androgen production
cortisol feeds back to HP but everything operates at a higher set point due to the excess ACTH secretion - higher level of ACTH production is maintained
what is an ectopic ACTH-producing tumour?
ectopic ACTH-producing tumour is located outside the pituitary gland
secretes ACTH leading to excess cortisol production
how does an ectopic ACTH-producing tumour affect cortisol levels? how does it affect the negative feedback loop?
ectopic ACTH stimulates the adrenal glands to produce high levels of cortisol and adrenal androgens
negative feedback to HP - suppresses HP CRH and ACTH, but the ectopic source of ACTH isn’t affected; bypasses the negative feedback loop and continues secreting ACTH
what distinguishes the negative feedback mechanism in ectopic ACTH production from Cushing’s disease?
ectopic ACTH production = negative feedback from cortisol suppresses pituitary ACTH release, but the ectopic source of ACTH continues to stimulate the adrenal glands, bypassing the neg. feedback
Cushing’s disease = negative feedback loop is maintained but everything is maintained at a higher set point due to the pituitary ACTH secreting adenoma
four causes of Cushing’s disease?
iatrogenic = prolonged use of glucocorticoid therapy/meds
Cushing’s disease – anterior pituitary ACTH secreting tumour
ectopic ACTH-secreting tumour
adrenal adenoma secreting high cortisol (primary Cushing’s syndrome)
what characterizes primary Cushing’s syndrome?
adrenal dysfunction, often due to an adrenal adenoma, leading to excessive cortisol production
how does increased cortisol production affect the HPA axis?
elevated cortisol levels from adrenal dysfunction increase negative feedback on HP - decreases ACTH
what test can establish the cause of Cushing’s syndrome?
dexamethasone suppression test
what is the dexamethasone suppression test?
involves administering a synthetic glucocorticoid - dexamethasone = acts on glucocorticoid receptors
suppresses cortisol production by activating HPA axis negative feedback
how does the high dose dexamethasone test help establish the cause for Cushing’s syndrome?
high dose dexamethasone suppression test carried out for 4 nights, measuring cortisol the following morning
in Cushing’s disease = high-dose dexamethasone suppresses cortisol production after several days due to the higher set point of the negative feedback loop
in ectopic ACTH = cortisol suppression doesn’t occur even with high doses, indicates a non-pituitary source of ACTH
